The use of imagery to treat illness is one of the oldest medical practices. Nevertheless, the mechanism of the treatment remains unknown. Recent brain imaging studies suggest that underlying the functional nature of mental imagery may be the overlapping neurocognitive operations that support imagination, perception, and action. Acupuncture is an ancient invasive therapeutic method. Previous studies have shown that both the experience of acupuncture needle stimulation and the visualization of acupuncture needle stimulation can provoke overlapping brain activation, which suggests that visualizing or imagining acupuncture may achieve therapeutic effects through a brain pathway similar to actual acupuncture treatment. This application will investigate the underlying brain mechanisms of video-guided acupuncture imagery treatment (VGAIT), a novel mind-body treatment modality. In this treatment, subjects will watch a video of acupuncture previously administered on their own bodies and imagine this prior treatment being concurrently applied. In the R61 phase, using a crossover design and functional magnetic resonance imaging (fMRI), we will investigate the cortical fMRI signal changes and resting state functional connectivity changes evoked by 1) VGAIT, 2) VGAIT control condition (subjects will watch a video of a cotton swab touching specific points on their bodies and imagine it being concurrently applied), 3) verum acupuncture, and 4) sham acupuncture administered on healthy subjects. In the R33 phase, knee osteoarthritis (OA) patients will be recruited and randomized to one of four treatment groups for one month: 1) VGAIT, 2) a VGAIT control condition, 3) verum acupuncture, and 4) sham acupuncture. We will investigate the fMRI signal changes and resting state functional connectivity changes evoked by the different conditions. This project will facilitate the development of new mind-body intervention methods that can directly benefit patients suffering from chronic pain. It would be especially beneficial to elderly and disabled patients who have limited access to acupuncture and medical care and could benefit from self- administered, at-home treatment following acupuncture treatment sessions. Most importantly, a comparative investigation of imagery acupuncture, real acupuncture, and sham acupuncture will deepen our understanding of mind-body interaction, imagery treatment, acupuncture, and pain management.